Pourquoi Game of Thrones est un cas clinique

La série d'HBO déclenche une hystérie planétaire chaque saison depuis 2011. On a tenté d'expliquer cette frénésie avec l'aide de psychologues

HCMV triggers frequent and persistent UL40- specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognition

International audienceImmune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected cells and to prevent reactivation. CD8 T cells against HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized and they associate with efficient virus control. HLA-E-restricted CD8 T cells targeting HCMV UL40 signal peptides (HLA-E[UL40]) have recently emerged as a non-conventional T-cell response also observed in some hosts. The occurrence, specificity and features of HLA-E[UL40] CD8 T-cell responses remain mostly unknown. Here, we detected and quantified these responses in blood samples from healthy blood donors (n = 25) and kidney transplant recipients (n = 121) and we investigated the biological determinants involved in their occurrence. Longitudinal and phenotype ex vivo analyses were performed in comparison to HLA-A*02/pp65-specific CD8 T cells. Using a set of 11 HLA-E/UL40 peptide tetramers we demonstrated the presence of HLA-E[UL40] CD8 αβT cells in up to 32% of seropositive HCMV+ hosts that may represent up to 38% of total circulating CD8 T-cells at a time point suggesting a strong expansion post-infection. Host's HLA-A*02 allele, HLA-E *01:01/*01:03 genotype and sequence of the UL40 peptide from the infecting strain are major factors affecting the incidence of HLA-E[UL40] CD8 T cells. These cells are effector memory CD8 (CD45RA[high]RO[low], CCR7-, CD27-, CD28-) characterized by a low level of PD-1 expression. HLA-E[UL40] responses appear early post-infection and display a broad, unbiased, Vβ repertoire. Although induced in HCMV strain-dependent, UL40[15-23]-specific manner, HLA-E[UL40] CD8 T cells are reactive toward a broader set of nonapeptides varying in 1-3 residues including most HLA-I signal peptides. Thus, HCMV induces strong and lifelong lasting HLA-E[UL40] CD8 T cells with potential allogeneic or/and autologous reactivity that take place selectively in at least a third of infections according to virus strain and host HLA concordance

Libres variations sur le sacré dans la littérature du xxe siècle

Cet ouvrage étudie la persistance du sacré dans la littérature après la crise religieuse qui a affecté le XXe siècle, siècle marqué par le mot célèbre de Nietzsche sur la « mort de Dieu » et par le silence divin à Auchwitz

Celebrating the 20th anniversary of the first Xanthomonas genome sequences – how genomics revolutionized taxonomy, provided insight into the emergence of pathogenic bacteria, enabled new fundamental discoveries and helped developing novel control measures – a perspective from the French network on Xanthomonads

International audienceIn this Opinion paper, members of the French Network on Xanthomonads give their personal view on what they consider to be some of the groundbreaking discoveries in the field of molecular plant pathology over the past 20 years. By celebrating the 20th anniversary of the first Xanthomonas genome sequences, they explain how genomics revolutionized taxonomy, provided insight into the emergence of pathogenic bacteria, enabled new fundamental discoveries and contributed to the development of novel control measures. Collectively, such new, genomics-enabled perspective will help to ensure sustainable agriculture and conservation of our environment in the future

Patient’s characteristics.

<p>Patient’s characteristics.</p

Sequences of UL40_15-23 peptide in the infecting HCMV strains.

<p>Sequences of UL40_15-23 peptide in the infecting HCMV strains.</p

Potential cross-recognition of autologous and allogeneic HLA-I signal peptides by HLA-E_UL40 CD8 T cells.

<p>PBMCs were isolated from freshly or prospectively collected blood samples at M12 post-transplantation issued from healthy donors (HV, n = 25) or from kidney transplant recipients (KTR, n = 119), respectively. <i>Ex vivo</i> detection of HLA-E_UL40 CD8 T and HLA-A*02_pp65-specific CD8 T cells was performed using flow cytometry by selecting CD3⁺ CD8α⁺ TCRγδ^- tetramer⁺ cells on PBMCs. Eight different HLA-E_UL40 tetramers were used independently. (A) Percentage of circulating anti-HCMV CD8 T cells in blood detected using the various HLA-E_UL40 (blue) and HLA-A*02_pp65 (in red) tetramers in HV and KTR. For each tetramer/peptide, the number of individuals with a given CD8 T-cell response is indicated. (B) Diversity and magnitude of the HLA-E_UL40 CD8 T-cell responses in KTR and HV. HLA-E_UL40 CD8 T-cell responses appear in blue and colour intensity is proportional to the percentage of HLA-E_UL40 CD8 T cells. (C) Classification of the HLA-E_UL40 CD8 T-cell responses in HCMV⁺ hosts according to possible recognition of self (orange), donor-specific allogeneic (green) or both (violet) (n = 31, 23 KTR and 8 HV). Grey boxes show HLA-I signal peptides which are not derived from the recipient, nor from the donor. Asterisks indicate peptides with underestimated information due to a lack of HLA-C genotyping.</p

Frequency of unconventional HLA-E_UL40 CD8 T-cell responses compared to conventional HLA-A*02_pp65 CD8 T-cell responses in HCMV⁺ kidney transplant recipients and healthy volunteers.

<p>PBMCs were isolated from freshly or prospectively harvested at M12 post-transplantation blood samples issued from healthy donors (HV) or from kidney transplant recipients (KTR), respectively. <i>Ex vivo</i> detection of HLA-E_UL40 CD8 T and HLA-A*02_pp65 CD8 T cells was performed using flow cytometry by selecting CD3⁺ CD8α⁺ TCRγδ^- tetramer⁺ cells on PBMCs. Detection threshold was 0.1% of total CD8 αβT cells and kidney transplant recipients and healthy volunteers bearing ≥0.1% of HLA-E_UL40 CD8 T cells (in blue) or ≥0.1% HLA-A*02_pp65 CD8 T cells (in red) were considered as positive. Detection of both types of CD8 T-cell responses are indicated in violet. Absence of detection is shown in light grey in HCMV^- recipients and dark grey for HCMV⁺ hosts. Data shown are the number of individuals that display anti-HCMV CD8 T-cell responses. Frequencies of the CD8 T-cell subsets were calculated among subgroups for all (total), non HLA-A*02 and HLA-A*02 individuals and expressed as percentages (%).</p

Time course analysis of the HLA-E_UL40 and HLA-A*02_pp65 CD8 T-cell anti-HCMV responses upon infection and patterns of activation markers.

<p>(A) Time course analysis of the HLA-E_UL40 and HLA-A*02_pp65 CD8 T-cell responses according to the HCMV viremia. PBMCs prospectively collected from M0 and M13 (#109) post-transplantation were retrospectively processed for the concomitant detection and quantification of anti-HCMV HLA-E_UL40 and HLA-A*02_pp65 CD8 T-cell responses upon infection. Three representative patterns of anti-HCMV CD8 T cell responses in 3 KTR (KTR#107, #108 and #109) are represented. (B) Analysis of T-cell activation. Expression of CD69 (left panel) and PD-1 (right panel) analysed on blood samples from KTR#107, #108 and #109. Facs histogram overlays represent the % of expression for the activation markers CD69 and PD-1 among CD3⁺ CD8α⁺ TCRγδ^- tetramers⁺ cells, for HLA-E_UL40 (in blue) and HLA-A*02_pp65 (in red) anti-HCMV CD8 T-cell responses at M6 post-transplantation. (C) Comparative analysis of CD69 (left panel) and PD-1 (right panel) expression on HLA-E_UL40 (n = 4 hosts) and HLA-A*02_pp65 (n = 8 hosts) CD8 T cells investigated at M6 post-transplantation. <i>P</i> values were calculated using a Mann Whitney test.</p